The effects of tilisolol on ischemic myocardial energy and carbohydrate metabolism were examined, and compared with those of propranolol. Ischemia was induced by ligating the left anterior descending coronary artery for 3 or 30 min in anesthetized open-chest dogs, 5 min after saline, tilisolol (0.2 mg.kg-1, i.v.), or propranolol (1 mg.kg-1, i.v.) injection. During ischemia, the myocardial energy stores were depleted, and the levels of glycolytic intermediates were altered, associated with ST segment elevation and TQ segment depression of the epicardial electrocardiogram. Tilisolol prevented the myocardial energy depletion and alterations of carbohydrate metabolism caused by 3 min of ischemia, to the same extent as did propranolol. Even 30 min after ischemia, the prevention of these ischemic changes was sustained by tilisolol, but not by propranolol. Tilisolol briefly reduced the ST segment elevation and TQ segment depression induced by ischemia. These results suggest that the protective effects of tilisolol on the ischemic myocardium are more potent and long-lasting than those of propranolol.